PMID- 34575445
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211001
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 13
IP  - 9
DP  - 2021 Aug 31
TI  - Design of Experiments to Achieve an Efficient Chitosan-Based DNA Vaccine Delivery 
      System.
LID - 10.3390/pharmaceutics13091369 [doi]
LID - 1369
AB  - In current times, DNA vaccines are seen as a promising approach to treat and 
      prevent diseases, such as virus infections and cancer. Aiming at the production 
      of a functional and effective plasmid DNA (pDNA) delivery system, four chitosan 
      polymers, differing in the molecular weight, were studied using the design of 
      experiments (DoE) tool. These gene delivery systems were formulated by ionotropic 
      gelation and exploring the chitosan and TPP concentrations as DoE inputs to 
      maximize the nanoparticle positive charge and minimize their size and 
      polydispersity index (PDI) as DoE outputs. The obtained linear and quadratic 
      models were statistically significant (p-value < 0.05) and non-significant lack 
      of fit, with suitable coefficient of determination and the respective optimal 
      points successfully validated. Furthermore, morphology, stability and 
      cytotoxicity assays were performed to evaluate the endurance of these systems 
      over time and their further potential for future in vitro studies. The subsequent 
      optimization process was successful achieved for the delivery systems based on 
      the four chitosan polymers, in which the smallest particle size was obtained for 
      the carrier containing the 5 kDa chitosan (~82 nm), while the nanosystem prepared 
      with the high molecular weight (HMW) chitosan displayed the highest zeta 
      potential (~+26.8 mV). Delivery systems were stable in the formulation buffer 
      after a month and did not exhibit toxicity for the cells. In this sense, DoE 
      revealed to be a powerful tool to explore and tailor the characteristics of 
      chitosan/pDNA nanosystems significantly contributing to unraveling an optimum 
      carrier for advancing the DNA vaccines delivery field.
FAU - Rodolfo, Carlos
AU  - Rodolfo C
AD  - CICS-UBI-Health Science Research Centre, University of Beira Interior, Av. 
      Infante D. Henrique, 6200-506 Covilha, Portugal.
FAU - Eusebio, Dalinda
AU  - Eusebio D
AD  - CICS-UBI-Health Science Research Centre, University of Beira Interior, Av. 
      Infante D. Henrique, 6200-506 Covilha, Portugal.
FAU - Ventura, Cathy
AU  - Ventura C
AD  - CICS-UBI-Health Science Research Centre, University of Beira Interior, Av. 
      Infante D. Henrique, 6200-506 Covilha, Portugal.
FAU - Nunes, Renato
AU  - Nunes R
AD  - CICS-UBI-Health Science Research Centre, University of Beira Interior, Av. 
      Infante D. Henrique, 6200-506 Covilha, Portugal.
FAU - Florindo, Helena F
AU  - Florindo HF
AD  - Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, 
      Universidade de Lisboa, 1649-003 Lisbon, Portugal.
FAU - Costa, Diana
AU  - Costa D
AD  - CICS-UBI-Health Science Research Centre, University of Beira Interior, Av. 
      Infante D. Henrique, 6200-506 Covilha, Portugal.
FAU - Sousa, Angela
AU  - Sousa A
AUID- ORCID: 0000-0001-9155-7581
AD  - CICS-UBI-Health Science Research Centre, University of Beira Interior, Av. 
      Infante D. Henrique, 6200-506 Covilha, Portugal.
LA  - eng
GR  - UIDB/00709/2020/Fundacao para a Ciencia e a Tecnologia/
GR  - 2020.10201.BD/Fundacao para a Ciencia e a Tecnologia/
GR  - IF/01459/2015/Fundacao para a Ciencia e a Tecnologia/
PT  - Journal Article
DEP - 20210831
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC8471690
OTO - NOTNLM
OT  - DNA vaccine
OT  - HPV
OT  - chitosan polymers
OT  - delivery systems
OT  - design of experiments
COIS- The authors declare no conflict of interest.
EDAT- 2021/09/29 06:00
MHDA- 2021/09/29 06:01
PMCR- 2021/08/31
CRDT- 2021/09/28 01:15
PHST- 2021/07/23 00:00 [received]
PHST- 2021/08/18 00:00 [revised]
PHST- 2021/08/28 00:00 [accepted]
PHST- 2021/09/28 01:15 [entrez]
PHST- 2021/09/29 06:00 [pubmed]
PHST- 2021/09/29 06:01 [medline]
PHST- 2021/08/31 00:00 [pmc-release]
AID - pharmaceutics13091369 [pii]
AID - pharmaceutics-13-01369 [pii]
AID - 10.3390/pharmaceutics13091369 [doi]
PST - epublish
SO  - Pharmaceutics. 2021 Aug 31;13(9):1369. doi: 10.3390/pharmaceutics13091369.